An investigation of blood-tissue exchange of plasma proteins and other large molecules in is proposed. Its goal is to find out how these substances, especially albumin and immunoglobulins, are transported across microvascular ("capillary") endothelium: what pathways are involved and what transport processes are responsible. A prime objective is to evaluate the roles of dissipative and convective transport mechanisms in microvascular beds of individual organs and tissues. These goals are approached by comparing blood-tissue clearances of selected tracer macromolecules differing in size, electrical charge and chemical configuration, and by determining the relation between solute clearances and volume flow. Normal animals and animal models of abnormal states will be studied. Among the latter are plasma volume expansion and contraction, analbuminemia and various forms of microvascular injury. The effects of several hormones thought to influence microvascular permeability to macromolecules will also be studied. These include atrial natriuretic peptide (ANP), vasopressin angiotensin and norepinephrine. The role of extracapillary forces arising in injured tissues on production of edema and protein leakage will be evaluated by in vitro and in vivo experiments. These investigations will further understanding of how plasma and interstitial fluid volumes are controlled under normal conditions, and of how these control mechanisms are affected by blood volume expansion or reduction, or in anaphylactoid or other inflammatory disturbances. They are directed toward identification of more effective means of intervention to reduce fluid and protein leakage from the vascular system and restore normal fluid balance between plasma and interstitial fluid compartments when disturbances of fluid and protein transport occur.